Abstract

A statistical-mechanical treatment of the molecular binding into lipidmembrane is presented in combination with molecular simulation. The membranesolution is viewed as an inhomogeneous, mixed solventsystem, and the free energy of solvation of a solute in membrane is computed with a realistic set of potential functions by the method of energy representation. Carbon monoxide, carbon dioxide, benzene, and ethylbenzene are adopted as model solutes to analyze the binding into 1,2-dimyristoyl--glycero-3-phosphatidylcholine (DMPC) membrane. It is shown that the membrane inside is more favorable than bulk water and that the solute distribution is diffuse throughout the membrane inside. The membrane-water partition coefficient is then constructed with the help of the Kirkwood-Buff theory from the solvation free energy obtained separately in the hydrophobic, glycerol, headgroup, and aqueous regions. To discuss the role of repulsive and attractive interactions, the solvation free energy is partitioned into the DMPC and water contributions and the effect of water to stabilize the benzene and ethylbenzene solutes within the membrane is pointed out.

Received 04 December 2007Accepted 10 April 2008Published online 22 May 2008

Acknowledgments:

This work is supported by the Grant-in-Aid for Scientific Research (No. 18350004) from the Japan Society for the Promotion of Science and by the Grants-in-Aid for Scientific Research on Priority Areas (Nos. 15076205 and 20038034) and the Nanoscience Program of the Next-Generation Supercomputing Project from the Ministry of Education, Culture, Sports, Science, and Technology. N.M. is also grateful for a grant from the Association for the Progress of New Chemistry, a grant from the Suntory Institute for Bioorganic Research, and a generous allocation of computation time from the Supercomputer Laboratory of Institute for Chemical Research, Kyoto University.